We have found the menopause produced by removing the ovaries makes an infection prolonged when inoculating bacteria causing bladder infection. However, in similar menopausal females kidney infections are not affected by menopause when the bacteria are nephropathogenic. The studies of infection in aged monkeys with normal menopause are nearing conclusion now. If this is due to hormonal status, why? The incidence of urinary tract infections is high in elderly females. Cynomolgus monkeys were used to study the effect of surgical menopause, using E. coli with different tip protein epitopes of P-fimbriae. E. coli DS17 in humans contains Class II epitope of tip protein of P-fimbriae is associated with acute pyelonephritis. E. coli DS17-1 contains Class III tip protein epitope of P-fimbriae and is associated with cystitis. E. coli 1x109 cfu/ml in 0.1ml was inoculated into the urethra of female monkeys. We compared cycling females to animals after bilateral oophorectomy. Bacteriuria with strain DS17-1 lasted 1 week and was not affected by oophorectomy. Bacteriuria with DS17 in cycling animals was for 21 days but in those with oophorectomy it lasted over a month. A highly significant difference was noted in pathology. Following oophorectomy 18 of 20 kidneys showed chronic pyelonephritis, while in cycling animals only 6 of 20 kidneys were involved. Serum antibody titers were as usual with cystitis from animals inoculated with DS17-1 with mean P titers of 1 to 5,000 as opposed to 1 to 20,000 in cycling female animals and 1 to 100,000 in animals oophorectomized following infection with DS17. The latter was consistent with the prolonged bacteriuria and renal pathology from this E. coli. Bacterial adherence to vaginal cells was much more marked in oophorectomized animals than animals with normal hormonal status. Urethral inoculation of E. coli containing Class II epitope of the tip protein of P fimbriae led to acute and chronic pyelonephritis, and E. coli containing the Class III tip epitope of P-fimbriae led to cystitis. Hormonal status and bacterial adherence were shown to be an important factor in these findings, supporting hormone replacement following menopause.